INFLUENCE OF DROLOXIFENE (3-HYDROXYTAMOXIFEN), 40 MG DAILY, ON PLASMAGONADOTROPINS, SEX-HORMONE BINDING GLOBULIN AND ESTROGEN-LEVELS IN POSTMENOPAUSAL BREAST-CANCER PATIENTS

Droloxifene (3-hydroxytamoxifen) is a novel antiestrogen currently und ergoing clinical investigations for treatment of breast cancer patient s. We measured plasma levels of sex hormone binding globulin (SHBG) an d the gonadotrophins (LH and FSH) at baseline and after 3 months on tr eatment in a group of fourteen postmenopausal women treated with drolo xifene 40 mg daily. Plasma levels of estrone (E(1)), estradiol (E(2)) and estrone sulphate (E(1)S) were measured in a subgroup of eight pati ents. Plasma SHBG increased during treatment with droloxifene by a mea n value of 16.6% (P < 0.05), while plasma levels of LH and FSH decreas ed by a mean value of 15.7% (n.s.) and 18.1% (P < 0.05), respectively. Plasma levels of E(2) and E(1) fell slightly (mean decrease 19.4 and 16.7% respectively, n.s.). On the contrary, plasma levels of E(1)S inc reased by a mean value of 23.5% (P = 0.068). The ratio of E(1)S to E(1 ) and E(1)S to E(2) increased by a mean value of 48.3% (P < 0.025) and 53.2% (P < 0.025), respectively. The effect of droloxifene 40 mg dail y on plasma levels of SHBG resembles what is seen during treatment wit h tamoxifen but occurs to a smaller extent. Contrary to tamoxifen, dro loxifene caused a minor suppression of plasma LH levels, suggesting dr oloxifene to have less estrogen agonistic effects on the pituitary.